Loss of expression of the tumor suppressor CEACAM1 links different hereditary colorectal carcinoma sub-types to the genesis of sporadic colorectal carcinoma

According to their carcinogenesis, colorectal cancer (CRC) subtypes show distinct molecular parameters. Hereditary non-polypous colorectal cancer (HNPCC) is the most common inherited CRC characterized by clinical criteria and confirmed microsatellite instability (MSI). Interestingly, a recently identified subtype, familial colorectal cancer type X (FCC-X), shows the same clinical criteria but microsatellite stability (MSS). CEACAM1 is a known tumor suppressor that regulates apoptosis in colon cells, and its loss is one of the most frequent events in early tumorigenesis of CRC. Therefore its loss may characterize precursor colon cells prior to neoplastic transformation. We analyzed tumor specimens of HNPCC and FCC-X patients in order to investigate whether there is a loss of CEACAM1 expression analogous to sporadic CRC and whether the expression of CEACAM1 would distinguish between these tumor entities. No differences in CEACAM1 expression were noted between HNPPC (n = 38) and FCC-X (n = 30) tumors. CEACAM1 was reduced in near-identical frequencies in 36/38 (95%) HNPCC and 29/30 (97%) FCC-X. This is the first report to demonstrate the loss of CEACAM1 expression in hereditary CRC. There was no difference between HNPCC and FCC-X. The frequency of expression loss was comparable to sporadic CRC, indicating that loss of CEACAM1 is an early event in colorectal tumorigenesis linking the genesis of sporadic and hereditary CRC

Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice

BACKGROUND: Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. METHODOLOGY: ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano. PRINCIPAL FINDINGS: After a single injection of ExiTron nano the contrast of liver and spleen peaked after 4-8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks. CONCLUSIONS: The nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast

Three-Dimensional In Vivo Imaging of the Murine Liver: A Micro-Computed Tomography-Based Anatomical Study

Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver

The proteolytic activity of separase in BCR-ABL-positive cells is increased by imatinib.

Separase, an endopeptidase required for the separation of sister-chromatides in mitotic anaphase, triggers centriole disengagement during centrosome duplication. In cancer, separase is frequently overexpressed, pointing to a functional role as an aneuploidy promoter associated with centrosomal amplification and genomic instability. Recently, we have shown that centrosomal amplification and subsequent chromosomal aberrations are a hallmark of chronic myeloid leukemia (CML), increasing from chronic phase (CP) toward blast crisis (BC). Moreover, a functional linkage of p210BCR-ABL tyrosine kinase activity with centrosomal amplification and clonal evolution has been established in long-term cell culture experiments. Unexpectedly, therapeutic doses of imatinib (IM) did not counteract; instead induced similar centrosomal alterations in vitro. We investigated the influence of IM and p210BCR-ABL on Separase as a potential driver of centrosomal amplification in CML. Short-term cell cultures of p210BCR-ABL-negative (NHDF, UROtsa, HL-60, U937), positive (K562, LAMA-84) and inducible (U937p210BCR-ABL/c6 (Tet-ON)) human cell lines were treated with therapeutic doses of IM and analyzed by qRT-PCR, Western blot analysis and quantitative Separase activity assays. Decreased Separase protein levels were observed in all cells treated with IM in a dose dependent manner. Accordingly, in all p210BCR-ABL-negative cell lines, decreased proteolytic activity of Separase was found. In contrast, p210BCR-ABL-positive cells showed increased Separase proteolytic activity. This activation of Separase was consistent with changes in the expression levels of Separase regulators (Separase phosphorylation at serine residue 1126, Securin, CyclinB1 and PP2A). Our data suggest that regulation of Separase in IM-treated BCR-ABL-positive cells occurs on both the protein expression and the proteolytic activity levels. Activation of Separase proteolytic activity exclusively in p210BCR-ABL-positive cells during IM treatment may act as a driving force for centrosomal amplification, contributing to genomic instability, clonal evolution and resistance in CML

Study of hydrated phases present in calcined paper sludge (metakaolinite)/saturated CaO dissolution system cured at 40 °C and 28 days of reaction

[EN] The present research is a part of an experimental study about obtaining recycled metakaolinite from a Spanish paper sludge waste as complementary cementing material. The mineral phases formation from paper sludge calcined at different temperatures (700, 750 and 800 °C) and two times of stay in the furnace (2 and 5 h) mixed with saturated lime dissolution are obtained mineral phases: C-S-H gel, stratlingite, tobermorite, hydrotalcite. The C-S-H gels generated in the first stages lose crystallinity and filled the existing holes between stratlingite and hydrotalcite. The different mineral evolves according to their stability fields toward crystalline aggregates more compact where the gels fill hollow.Peer reviewe

A shows a volume rendering of a mouse 30 minutes after i.v. injection of ExiTron nano 12000.

<p>B is a curved maximum intensity projection in coronal orientation of the same scan. A and B demonstrate the feasibility to perform CT angiography during the early intravascular phase of the tested contrast agent. Additionally, A and B show the early contrast agent uptake by the RES with increasing contrast of liver and spleen. C is a coronally oriented curved maximum intensity projection of a mouse that did not receive contrast agent.</p